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The accumulation of intraepithelial lymphocytes (IELs) is a histopathological feature of canine chronic enteropathy (CE), and IELs are considered the cells of origin of intestinal T-cell lymphoma (ITCL). However, the pathogenic mechanism of IEL activation in CE remains unclear. This study hypothesized that the expression of proinflammatory cytokines, associated with cytotoxic T/NK-cell activation, is upregulated in CE and ITCL, and examined the expression of IFN-γ , IL-2 , IL-12p35, IL-12p40 , IL-15 , and IL-21 and the downstream signal transducers and activators of transcription (STAT) pathway in the duodenal mucosa of dogs without lesions ( n = 11; NC), with IEL - CE ( n = 19; CE without intraepithelial lymphocytosis), IEL + CE ( n = 29; CE with intraepithelial lymphocytosis), and with ITCL ( n = 60). Quantitative polymerase chain reaction (PCR) revealed that IFN-γ and IL-21 were higher in IEL + CE than in IEL - CE or NC. Western blot revealed upregulation of STAT1 and STAT3 in IEL + CE. Double-labeling immunohistochemistry revealed a positive correlation between the Ki67 index of CD3 + T-cells and IFN-γ expression levels. Immunohistochemistry revealed a higher ratio of p-STAT1-positive villi in IEL + CE and ITCL than IEL - CE and NC, which positively correlated with IFN-γ expression levels. Among the 60 ITCL cases, neoplastic lymphocytes were immunopositive for p-STAT1 in 28 cases and p-STAT3 in 29 cases. These results suggest that IFN-γ and IL-21 contribute to the pathogenesis of IEL + CE, and IFN-γ may be involved in T-cell activation and mucosal injury in CE. STAT1 and STAT3 activation in ITCL cells suggests a role for the upregulation of the STAT pathway in the pathogenesis of ITCL., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The clinical significance of severe infiltration of small intraepithelial lymphocytes (IEL) and the results of polymerase chain reaction for antigen receptor rearrangement (PARR) in dogs with chronic enteropathy (CE) and small-cell lymphoma (SCL) are controversial. This cohort study aimed to evaluate the prognostic significance of the IEL and PARR results in dogs with CE or SCL. Although definitive diagnostic histopathological criteria for SCL in dogs have yet to be established, dogs with the histopathological findings of severe IEL infiltration were diagnosed with SCL in this study. One hundred and nineteen dogs were recruited, with 23 dogs classified as having SCL and 96 dogs as having CE. The positive rate of PARR was 59.6 % (71/119) in the duodenum and 57.7 % (64/111) in the ileum. Subsequently, three dogs with SCL and four dogs with CE developed large-cell lymphoma (LCL). The median overall survival (OS) of dogs with SCL was 700 days (range, 6-1410 days), and that of dogs with CE was not reached. In the log-rank test, shorter OS was observed in cases with histopathological SCL (P = 0.035), clonal TCRγ rearrangement in the duodenum (P = 0.012), and clonal IgH rearrangement in the ileum (P < 0.0001). The Cox proportional hazards model adjusted for sex and age showed that histopathological SCL (hazard ratio [HR] 1.74; 95 % confidence interval [CI], 0.83-3.65), duodenal clonal TCRγ rearrangement (HR, 1.80; 95 % CI, 0.86-3.75), and ileal clonal IgH rearrangement (HR, 2.28; 95 % CI, 0.92-5.70) could shorten overall survival, although their 95 % CIs included 1.0. These results indicate that severe IEL infiltration could be a useful histopathological feature for diagnosing SCL, and clonality-positive results could be a negative prognostic factor in dogs with CE. Furthermore, the development of LCL should be carefully monitored in dogs with CE and SCL.., Competing Interests: Declaration of Competing Interest Y. Takeuchi has received lecture fees from SAS Institute Japan Ltd. The authors declare no competing interests relevant to this study., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Gallbladder mucocele (GBM) is a common biliary disorder in dogs that can be categorized into 6 types, but the value of this classification scheme remains unknown. Cholecystectomy is associated with high death rates and warrants additional interrogation., Objectives: Investigate the clinical value of ultrasonographic diagnosis of type of GBM and identify prognostic factors in dogs with GBM undergoing cholecystectomy., Animals: Two hundred sixteen dogs., Methods: Retrospective cohort study. Dogs with GBM diagnosed from 2014 to 2019 at 6 veterinary referral hospitals in Asia. Ultrasonogram images were reviewed and a GBM type (ie, types I-VI) assigned., Results: Dogs with GBM type V as compared to I (OR, 8.6; 95% CI, 2.6-27.8; P < .001) and III (OR, 10.0; 95% CI, 2.5-40.8; P = .001), and dogs with type VI compared to I (OR, 10.5; 95% CI, 1.8-61.2; P = .009) and III (OR, 12.3; 95% CI, 1.8-83.9; P = .01) were more likely to exhibit signs of biliary tract disease. Independent predictors of death after cholecystectomy included age (OR, 2.81; 95% CI, 1.41-5.59; P = .003) and intraoperative systolic blood pressure (SBP) nadir. There was an interaction between SBP nadir and gallbladder rupture; SBP nadir in dogs with (OR, 0.92; 95% CI, 0.89-0.94; P < .001) and without (OR, 0.88; 95% CI, 0.82-0.93; P < .001) gallbladder rupture., Conclusion and Clinical Importance: Increasing developmental stage of GBM could be associated with an increased likelihood of biliary tract related clinical signs. Nadir SBP deserves further investigation as a prognostic or potentially modifiable variable, particularly in the presence of gallbladder rupture., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Human enteropathy-associated T-cell lymphoma (EATL) is considered to be derived from intraepithelial lymphocytes (IELs); however, the origin of canine intestinal T-cell lymphoma (ITCL) remains unclear. Histological, immunohistochemical, and clonality examinations were performed using endoscopically collected canine duodenum samples of mucosal lesions of chronic enteropathy (CE; 73 cases) and ITCL without transmural neoplastic mass lesions (64 cases). Histopathological examinations revealed the intraepithelial accumulation of lymphocytes (called "intraepithelial lymphocytosis") in 54/73 CE cases (74%) and the epitheliotropism of neoplastic lymphocytes in 63/64 ITCL cases (98%). Immunohistochemically, IELs in CE with intraepithelial lymphocytosis (IEL + CE) were diffusely immunopositive for CD3, with scattered immunopositivity for CD5, CD8, CD20, and granzyme B (GRB). The percentage of CD8 + in CD3 + IELs was significantly lower in IEL + CE than in CE without intraepithelial lymphocytosis (IEL - CE). Double-labeling immunohistochemistry revealed a high percentage of GRB expression in CD8 - IEL among IEL + CE. Among 64 ITCL cases, CD3 was immunopositive in 64 (100%), CD5 in 22 (34%), CD8 in 8 (13%), CD20 in 12 (19%), CD30 in 13 (20%), and GRB in 49 (77%). In CD3 + cells, Ki67 immunopositivity was highest in ITCL, intermediate in IEL + CE, and lower in IEL - CE. A clonal TCR gene rearrangement was detected in 1/19 IEL - CE cases (5%), 15/54 IEL + CE (28%), and 38/58 ITCL (66%). These results indicate that the immunophenotype of canine ITCL (CD8 - GRB + ) is similar to that of the increased IELs in CE. The high proliferative activity and clonality of T cells in IEL + CE suggest that canine ITCL originates from these IELs, similar to human EATL.

Wnt/beta-catenin signaling, E-cadherin and p53 reportedly play important roles in the development and/or progression of human gastrointestinal cancer. The present study evaluated the roles of beta-catenin, E-cadherin and p53 in canine gastrointestinal tumors. Endoscopic biopsy or surgically resected samples, a total of 131, including 38 gastric, 13 small intestinal and 80 large intestinal tumors, were obtained from 95 dogs. Those specimens were examined pathologically. Immunohistochemically, nuclear beta-catenin expression was found in 88% (42/48) of polypoid type adenocarcinomas. Most cases of non-polypoid type adenocarcinomas lacked nuclear expression of beta-catenin with the exception of one case (6%, 1/17). Nuclear beta-catenin expression was not observed in signet ring cell carcinomas (0/15), mucinous adenocarcinomas (0/7) and undifferentiated carcinomas (0/4). The findings indicate that nuclear translocation of beta-catenin is closely related to the development of polypoid type adenocarcinomas but not that of non-polypoid type malignant tumors. The immunoreactivity of E-cadherin for tumor cells tended to decline overall in most of cases including benign tumors. Significant immunoreactivity for p53 was not found in 61% of tumors examined (80/131), including malignant tumors (63%, 57/91), while intense p53-immunoreactivity was rarely found in a few cases of malignant tumors (8%, 7/91). We could not conclude clearly significant correlations between histopathological tumor types and immunohistochemical results of E-cadherin or p53. This paper indicates the importance of the nuclear translocation of beta-catenin for the tumorigenesis of canine intestinal polypoid type adenocarcinomas, especially in the colorectum.

Human enteropathy-associated T-cell lymphoma (EATL) is classified into 2 distinct subgroups based on their phenotypes (type I and type II). Canine intestinal T-cell lymphoma can be morphologically classified into large and small cell lymphomas (LCL and SCL, respectively). Their association with human EATL or immunohistochemical and biological features has not been well characterized. In this study, the immunohistochemical profiles of 17 cases of LCL and 33 cases of SCL were evaluated with markers used for human EATL classification. Morphologically, LCL was characterized by sheet-like proliferation of large to moderately sized neoplastic lymphocytes, with scant clear cytoplasm and pleomorphic, irregularly shaped nuclei containing distinctive nucleoli and scattered chromatin. In contrast, SCL was characterized by the proliferation of monomorphic small neoplastic lymphocytes, accompanied by infiltration of nonneoplastic plasma cells. Interestingly, 8 cases demonstrated mixed LCL and SCL morphologies. Granular cytoplasmic expression of granzyme B was observed in most LCL and SCL cases. Membranous expression of CD56 was demonstrated in only 2 of 17 LCL and 0 of 33 SCL cases. Coexpression of CD20 by neoplastic T cells was observed in more SCL cases (16/33; 48%) than LCL cases (1/17; 6%). The CD56-positive cells in 2 cases were negative for CD20. Although canine LCL shares common features with human EATL type I, canine SCL cells and human EATL type II differ in their immunophenotype. Canine intestinal T-cell lymphoma had a homogeneous immunophenotype regardless of cell morphology. The findings of this study may indicate large cell transformation of SCL rather than 2 distinct entities.

Intestinal T-cell lymphoma is being more frequently diagnosed in dogs owing to the wide availability of endoscopy and clonality analysis in veterinary medicine. However, no epidemiological study on intestinal T-cell lymphoma has been previously performed, and hence, information about dog breed, age and sex distributions of intestinal T-cell lymphoma has largely remained unclear. In this study, breed predisposition to canine intestinal T-cell lymphoma was determined by calculating odds ratios and 95% confidential intervals. Of the 43 breeds identified, 7 appeared to have an increased risk of developing intestinal T-cell lymphoma, including Shiba dogs, German shepherds, Cairn terriers, Boston terriers, Papillons, Pugs and Maltese. Immunohistochemistry of representative Shiba cases revealed ubiquitous cytotoxic immunophenotype in both large and small cell lymphomas. Interestingly, CD20 co-expression was observed in 11% of cases. It could potentially be aberrant expression of CD20 or neoplastic transformation of a normal subset of CD20-positive T-cells. A comparison of mean age between representative breeds revealed that Shiba dogs were slightly younger than Miniature Dachshunds (P < .05). However, there was no difference in survival between the 2 breeds. As Shiba dogs are predisposed to chronic enteropathy, there may be underlying inflammatory process contributing to lymphomagenesis of intestinal T-cell lymphoma in this breed. Our findings provide insights into the underlying pathogenesis of breed-specific canine intestinal T-cell lymphoma., (© 2018 John Wiley & Sons Ltd.)

Biopsy samples of colorectal polyps were collected and examined from 67 Miniature Dachshund dogs (including 35 cases with an additional biopsy). Histopathologic diagnoses of the initial biopsy samples were "inflammatory polyp" in 52 cases (78%), "adenoma" in 10 cases (15%), and "adenocarcinoma" in 5 cases (8%). Eight of 10 cases (80%) diagnosed as adenoma also had inflammatory polyp lesions in the same specimen. A second biopsy was performed in 25 cases (48%) initially diagnosed with inflammatory polyp. Pathologic diagnoses for the second biopsy were inflammatory polyp in 11 cases (44%), adenoma in 9 cases (36%), and adenocarcinoma in 5 cases (20%). The number of beta-catenin-positive nuclei in epithelial cells was significantly higher in adenoma (46%) and adenocarcinoma (75%) as compared with inflammatory polyp (6%). Normal epithelial cells and hyperplastic goblet cells in inflammatory polyps showed homogeneous positive cytoplasmic immunoreactivity for adenomatous polyposis coli (APC) antigen. However, APC expression was decreased in areas of intense nuclear beta-catenin expression in adenoma and adenocarcinoma lesions. Foci of cytokeratin 5/6-positive squamous cell-like neoplastic cells showed intense beta-catenin nuclear expression that was similar to squamous morules described in human colorectal tumors. The results of the present study suggest that the inflammatory polyp in Miniature Dachshunds is a progressive disease that may develop into adenoma and/or adenocarcinoma. In addition, immunohistochemical findings suggest that aberrations of APC and beta-catenin expression may be involved in tumor development within the inflammatory polyp lesions.

Molecular clonality analysis of T-cell receptor (TCR) genes for diagnosing T-cell lymphoma is widely used in veterinary medicine. However, differentiating chronic enteritis (CE) from intestinal lymphoma is challenging because of the incompatibility between histopathologic and clonality analysis results. On the basis of findings that canine intestinal T-cell lymphoma and celiac disease share some common features, we conducted serologic examinations in combination with histopathologic and T-cell receptor clonality analyses in 48 dogs diagnosed with either CE or intestinal lymphoma. Immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies against gliadin and tissue transglutaminase (tTG) were quantitatively measured using ELISA. The conditions were classified according to the histopathologic diagnosis, clonality analysis, and combined histopathologic/clonality analysis. Histopathologic analysis showed that dogs with intestinal lymphoma were likely to have high levels of serum IgA antibodies against gliadin and tTG, and serum IgG antibodies against tTG. No correlation between the diagnosed groups and control group was observed in the results of the clonality analysis and histopathologic/clonality analysis. It is interesting that dogs with intestinal lymphoma had a higher serum IgA titer against gliadin and tTG than did dogs with CE. These results suggest an association between repetitive inflammatory stimulation by gliadin peptides and subsequent intestinal lymphoma in dogs.

Epidemiological and pathological studies of Helicobacter spp. in canine stomachs in Japan were performed to investigate strain specific pathogenicity. Gastric biopsies from 144 dogs with gastrointestinal diseases were evaluated for the presence of Helicobacter spp. using genus and species specific PCRs for Helicobacter felis, Helicobacter bizzozeronii, Helicobacter heilmannii sensu stricto (s.s.) and Helicobacter pylori. PCR indicated that 50/144 (34.7%) dogs were infected with Helicobacter spp. Of the genus positive samples, 21/50 could not be amplified by any of the species specific PCRs. To investigate Helicobacter at the species level, partial ureAB gene sequences from 48/50 genus positive samples were determined; 47 strains were identified. Thirty-five strains from 45 cases were closely related to H. heilmannii s.s. (89-99% sequence similarity), seven strains from seven cases were closely related to H. bizzozeronii (95-99% sequence similarity), three strains from three cases were closely related to Helicobacter felis (86%, 98% and 99% sequence similarity), one strain from one case was closely related to Helicobacter salomonis (99% sequence similarity) and one strain from one case was closely related to H. pylori (99% sequence similarity). Dogs infected with Helicobacter spp. most similar to H. heilmannii s.s. had a higher frequency of moderate to severe gastritis than dogs negative for Helicobacter spp. (P=0.044). In conclusion, the predominant Helicobacter spp. detected in canine stomachs in our study were most closely related to H. heilmannii s.s. and displayed substantial genetic diversity. Infection with Helicobacter spp. may be associated with more severe gastritis in dogs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The histopathologic characteristics of colorectal inflammatory polyps that formed in Miniature Dachshunds were compared with those of other colorectal proliferative lesions, including adenomas and adenocarcinomas. Fifty-three colorectal polypoid lesions were histopathologically classified into inflammatory polyps (26 cases), adenoma (18 cases), and adenocarcinoma (9 cases). All 26 dogs that were diagnosed with inflammatory polyps were Miniature Dachshunds, indicating that colorectal inflammatory polyps exhibit a marked predilection for this breed. The inflammatory polyps had complex histopathologic features and were classified into 3 stages based on their epithelial composition. In early stage (stage 1), the polyps tended to exhibit a thickened mucosa containing hyperplastic goblet cells, dilated crypts filled with a large amount of mucus, and mild lymphocyte and macrophage infiltration. In later stages (stages 2 and 3), more severe neutrophil infiltration, interstitial mucus accumulation, granulation tissue, and occasional osteoid tissue were seen. Also, a few small foci of dysplastic epithelial cells were detected. The hyperplastic goblet cells, which were a major component of the epithelium of the inflammatory polyps, were positive for cytokeratin 20 (CK20), while the dysplastic epithelial cells found in inflammatory polyps (stage 3) and the tumor cells of the adenomas and adenocarcinomas were negative for CK20. These CK20-negative epithelial cells exhibited cytoplasmic and nuclear immunoreactivity for beta-catenin. In addition, the epithelial cells in the inflammatory polyps demonstrated significantly higher cyclooxygenase 2 and fibroblast growth factor 2 expression than did those of the adenomas and adenocarcinomas, suggesting that the arachidonate cascade is involved in the development of colorectal inflammatory polyps in miniature dachshunds., (© The Author(s) 2016.)

Inflammatory colorectal polyp (ICRP), common in miniature dachshunds, presents with hematochezia, tenesmus and mucoid feces. Although an 80% response rate has been reported when treated with prednisolone and cyclosporine, effective treatment is needed for the remaining 20% of ICRP dogs. Leflunomide is an immunosuppressive drug reported as effective in several immune-mediated diseases. In the present study, we retrospectively evaluated the efficacy and adverse effects of leflunomide in 15 ICRP dogs that were refractory to treatment with prednisolone and cyclosporine. Treatment efficacy was assessed by endoscopy, clinical symptoms and rectal palpation. Adverse effects were determined by clinical symptoms and blood testing during follow-up. The leflunomide treatment response rate was 93.3%. The median dosage of leflunomide and the median response time were 3 mg/kg (range: 1.7-4.0 mg/kg) and 35 days (range: 20-119 days), respectively. Adverse effects observed included lethargy (3 dogs), anorexia (1 dog), respiratory symptoms (1 dog), leukocytopenia (2 dogs), thrombocytopenia (1 dog), anemia (1 dog) and liver enzyme elevation (8 dogs). Most of the adverse effects improved with symptomatic treatment and leflunomide discontinuation or dosage reduction. In conclusion, leflunomide treatment is effective in ICRP dogs refractory to treatment with prednisolone and cyclosporine. Because several adverse effects were observed, close monitoring is needed during leflunomide treatment follow-up.

Ollulanus tricuspis is a small nematode parasite of the stomach, and its infection has been reported worldwide in cats but only one report in dogs as post-mortem diagnosis. Two dogs, kept in the Tokyo area, were presented for chronic vomiting. Chronic gastritis was diagnosed histologically, and many nematodes were detected in endoscopically-biopsied gastric samples and in the mucus of vomitus in both dogs. The parasites were small (<1 mm), and their morphological characteristics were consistent with those previously reported for O. tricuspis. The symptoms in one dog completely disappeared after anthelmintic therapy. To our knowledge, this is the first report describing ante-mortem diagnosis of spontaneous gastric O. tricuspis infection in dogs in which infectivity and pathogenicity of the nematode are suggested.

A 10-year-old castrated male mixed-breed dog exhibited vomiting, lethargy and anorexia. An abdominal ultrasound examination revealed a focal dilation of the abdominal aorta. The dog died 2 days after examination, and necropsy revealed a ruptured aneurysm at the abdominal aorta between the kidneys. Histological examination revealed severe granulomatous and necrotizing pan-arteritis with fungal organisms. Graphium species was identified through DNA sequence analysis of the PCR product from formalin-fixed paraffin-embedded samples. To our knowledge, this is the first report of aortic aneurysm caused by Graphium species in a dog. Sequence was submitted to the DNA Data Bank of Japan with the accession number LC007972.

Canine protein-losing enteropathy (PLE) is associated with severe gastrointestinal disorders and has a guarded to poor prognosis although little information is available regarding factors affecting prognosis. The purpose of this study was to identify the prognostic factors for survival of dogs with PLE. Ninety-two dogs diagnosed with PLE from 2006 to 2011 were included in a retrospective cohort study. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Variables recorded at the time of diagnosis were statistically analysed for possible prognostic factors in a univariate and multivariate Cox proportional hazard model. In the multivariate analysis, the predictors for mortality in dogs with PLE were more highly scored in terms of canine inflammatory bowel disease activity index (CIBDAI) (P = 0.0003), clonal rearrangement of lymphocyte antigen receptor genes (P = 0.003), and elevation of blood urea nitrogen (BUN) (P = 0.03). Using histopathological diagnosis, both small- and large-cell lymphomas were associated with significantly shorter survival times than chronic enteritis (CE) and intestinal lymphangiectasia (IL). Normalization of CIBDAI and plasma albumin concentration within 50 days of initial treatment was associated with a longer survival time. In conclusion, CIBDAI, clonal rearrangement of lymphocyte antigen receptor genes, histopathological diagnosis, and response to initial treatments would be valuable in separating the underlying causes and could be important in predicting prognosis in dogs with PLE., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Although definitive diagnosis of chronic enteropathy (CE) and gastrointestinal (GI) lymphoma requires histopathological evaluation of the GI tract, these conditions are often still difficult to differentiate from each other. Polymerase chain reaction (PCR) for antigen receptor gene rearrangements (PARR) has been applied recently as an adjunctive for diagnosis of lymphoid tumors; however, its clinical value in canine CE and GI lymphoma remains unclear. The purpose of this study was to investigate the relationship between PARR and histopathological diagnosis, degree of enteritis or lymphoma, and long-term prognosis in dogs, in order to evaluate the clinical significance of PARR. Endoscopic biopsy specimens obtained from 96 dogs with chronic enteritis (mild, n=14; moderate, n=20; marked, n=62) and 21 dogs with GI lymphoma were used. Clonality was observed in 51% of the animals with chronic enteritis; interestingly, it was found in 29% of those with only mild enteritis. In dogs with marked enteritis, the rate of PARR was higher in those with lymphocyte epitheliotropism than in those without epitheliotropism. The sensitivity of PARR in animals with GI lymphoma was 76%. There was no significant prognostic difference between chronic enteritis with or without clonal rearrangements. In contrast, dogs histopathologically diagnosed with marked enteritis had a significantly shorter survival time than did those with mild or moderate enteritis. While the significance of PARR in the diagnosis of GI lymphoma remains uncertain, the pathological roles of clonally expanding lymphocytes in canine CE should be investigated further., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Polymerase chain reaction (PCR) amplification to detect immunoglobulin heavy chain (IgH) and T cell receptor γ-chain (TCRγ) gene rearrangements has recently become widely used as part of the diagnostic strategy for lymphoid tumors in dogs. In this study, we constructed a multicolor GeneScan analytical system to improve the sensitivity and resolution of the clonality analysis of antigen receptor gene rearrangements in dogs. We used 7 reactions per sample, with 2 PCR conditions, to amplify IgH/TCRγ and control genes. By using multicolor-labeled primers, these 7 PCR products could be combined into 3 tubes before capillary electrophoresis. Clonal rearrangement of the IgH/TCRγ genes was detected in 93.3% of dogs with multicentric lymphoma and 84.6% of dogs with gastrointestinal lymphoma. Detection sensitivity of the clonally expanded cells in the background of normal peripheral blood mononuclear cells was 1-10%. The multicolor GeneScan analytical system developed here may prove to be helpful for the diagnosis of lymphoid tumors in dogs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Two miniature dachshunds, a 7-year-old neutered male and an 8-year-old male, presented with chronic hematochezia and tenesmus. A solitary pedunculated or multiple diffuse colorectal polyps were identified by colonoscopy and resected by polypectomy. Inflammatory colorectal polyps (ICRPs) were diagnosed according to histopathological findings. Both cases were treated with immunosuppressive therapy, and the clinical signs were resolved, although the colorectal polyps remained to some extent. Several months after the initial diagnosis, both cases presented with recurrence of hematochezia and enlargement of the polyps. A second colonoscopic polypectomy was performed, and adenoma was diagnosed histopathologically in both cases. ICRPs are a nonneoplastic disease, but their long-term prognosis is unknown. Careful follow-up seems to be important, and repetitive biopsy is recommended when growth of polyps is identified in miniature dachshunds with ICRPs.

Background: Although immunoglobulin A (IgA) plays a key role in regulating gut homeostasis, its role in canine inflammatory bowel disease (IBD) is unknown., Hypothesis: IgA expression may be altered in dogs with IBD, unlike that observed in healthy dogs and dogs with other gastrointestinal diseases., Animals: Thirty-seven dogs with IBD, 10 dogs with intestinal lymphoma, and 20 healthy dogs., Methods: Prospective study. IgA and IgG concentrations in serum, feces, and duodenal samples were measured by ELISA. IgA(+) cells in duodenal lamina propria and IgA(+) CD21(+) peripheral blood mononuclear cells (PBMCs) were examined by immunohistochemistry and flow cytometry, respectively. Duodenal expression of the IgA-inducing cytokine transforming growth factor β (TGF-β), B cell activating factor (BAFF), and a proliferation-inducing ligand (APRIL) was quantified by real-time RT-PCR., Results: Compared to healthy dogs, dogs with IBD had significantly decreased concentrations of IgA in fecal and duodenal samples. The number of IgA(+) CD21(+) PBMCs and IgA(+) cells in duodenal lamina propria was significantly lower in dogs with IBD than in healthy dogs or dogs with intestinal lymphoma. Duodenal BAFF and APRIL mRNA expression was significantly higher in IBD dogs than in the healthy controls. Duodenal TGF-β mRNA expression was significantly lower in dogs with IBD than in healthy dogs and dogs with intestinal lymphoma., Conclusions and Clinical Importance: IBD dogs have decreased IgA concentrations in feces and duodenum and fewer IgA(+) PBMCs, which might contribute to development of chronic enteritis in dogs with IBD., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Urea breath test (UBT) using an infrared spectral analyzer is widely used for non-invasive and rapid detection of gastric Helicobacter spp. in human, but not veterinary medicine. The main purposes of this study were to determine the reference range of the UBT in dogs and to evaluate its clinical usefulness. To address the first aim, 6 healthy laboratory beagles were subjected to UBT and upper gastrointestinal endoscopy. Gastric endoscopic biopsy samples from the antrum, corpus and fundus were examined for Helicobacter spp. by polymerase chain reaction (PCR) testing, rapid urease test (RUT), histology and cytology. Amoxicillin, metronidazole and omeprazole were given to infected dogs for 14 days, and dogs that became Helicobacter-negative were used to determine the reference range for UBT. To address the second aim, 32 canine patients underwent UBT before upper gastrointestinal endoscopy, and the sensitivity and specificity of UBT were calculated based on our newly determined reference range using PCR as the gold standard for detection of Helicobacter spp. Initially, all 6 laboratory beagles were infected in all gastric regions and became uninfected after eradication. The mean ± 2 SD UBT value after eradication was 0.6 ± 1.8‰, and the reference range for UBT was determined to be less than 2.5‰. UBT was completed successfully in 27 patients. Using our reference range, UBT displayed 89% (16/18) sensitivity and 89% (8/9) specificity, indicating that UBT was quite useful for the detection of gastric Helicobacter spp. infection in dogs.

Interleukin (IL)-1β is a key mediator of the inflammatory response. IL-1 receptor antagonist (IL-1Ra) regulates inflammation by functioning as an endogenous inhibitor of IL-1β. A disruption of the balance between IL-1β and IL-1Ra has been identified in human inflammatory bowel disease (IBD). The objective of this study was to determine whether there is an intestinal imbalance of IL-1β and IL-1Ra in canine IBD by comparing expression of IL-1β and IL-1Ra mRNA by real-time RT-PCR and expression of IL-1β and IL-1Ra protein by ELISA in 21 dogs with IBD, 15 dogs with intestinal lymphoma ('inflammatory' controls) and 20 healthy Beagles ('healthy' controls). A significant decrease in the intestinal IL-1Ra:IL-1β ratio of mRNA and protein was observed in IBD cases when compared with healthy control dogs. In contrast, a decrease in IL-1Ra:IL-1β ratio was not observed in dogs with intestinal lymphoma. The IL-1Ra:IL-1β protein ratio was negatively correlated with clinical severity in dogs with IBD. An intestinal imbalance between IL-1β and IL-1Ra production may play a role in the pathogenesis of canine IBD., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Previous report demonstrated that prokinetic agent mosapride has anti-ulcerogenic action in rat-indomethacin gastric mucosal injury model. Here, we assessed the prophylactic effect of mosapride on gastric mucosal injury and emptying disorder induced by prednisolone in dogs. Crossover study design was employed. Six healthy beagles were administered prednisolone alone (2 mg/kg, twice a day [BID] subcutaneously) and prednisolone with mosapride (1 mg/kg, BID, orally), followed by an interval of at least 6 weeks. In each treatment, gastric mucosal injury was scored endoscopically according to the modified Lanza scale, and gastric emptying was assessed with (13)C-octanoic acid breath test. The incidence of gastrointestinal adverse events was also investigated. Coadministration of mosapride with prednisolone significantly (P<0.05) reduced the gastric mucosal injury score (mean ± SD, 17.67 ± 6.96), compared with that of prednisolone treatment alone (25.50 ± 13.03). Prednisolone treatment delayed the half-emptying time (184 ± 45 min) compared with that of controls (137 ± 19 min), and coadministration of mosapride improved this gastric-emptying delay (143 ± 29 min). Furthermore, the incidence of the gastrointestinal adverse event vomiting became less frequent upon coadministration with mosapride. In addition to its prokinetic action, our study suggests that mosapride has an anti-ulcerogenic action in dogs. The use of mosapride in combination with prednisolone is effective for attenuating prednisolone-induced gastrointestinal adverse events.

The interaction between fractalkine/CX(3)CL1 and its receptor CX(3)CR1 has been reported to play an important role in various human inflammatory diseases, including inflammatory bowel disease (IBD) mediated by lymphocyte chemoattraction. The objective of this study was to investigate the role of fractalkine and CX(3)CR1 in lymphocyte migration in canine IBD. IBD was diagnosed in 34 dogs, and 19 healthy beagles were used as normal controls. We quantified intestinal mRNA and protein expression of fractalkine and CX(3)CR1 by real-time RT-PCR and ELISA, respectively, and examined the localization of fractalkine in canine intestine by immunohistochemistry. The expression of CX(3)CR1 and surface antigens on peripheral blood mononuclear cells (PBMCs) and intraepithelial lymphocytes (IELs) was analyzed by flow cytometry. Intestinal fractalkine and CX(3)CR1 mRNA was significantly up-regulated in IBD dogs compared with the healthy control dogs. In addition, fractalkine expression on intestinal epithelial cells was significantly increased in the intestinal mucosa of IBD dogs compared with the healthy dogs. CX(3)CR1(+) PBMCs were significantly elevated in IBD dogs and positively correlated with the histopathological severity of IELs infiltration. These CX(3)CR1(+) PBMCs predominantly expressed markers for cytotoxic T cells. Almost all IELs expressed CD3, and the majority of cells expressed CD8 rather than CD4, which was analogous to the CX(3)CR1(+) PBMCs. These results suggest that the fractalkine-CX(3)CR1 interaction may contribute to the pathogenesis of canine IBD through migration of IELs., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Little information is available on the relationship between computed tomography (CT) imaging findings and the pathologic diagnosis of canine hepatic tumors. Our purpose was to clarify the characteristic features of CT findings in liver tumors in dogs. Data from 33 dogs with either a hepatocellular carcinoma, n = 14, hepatocellular adenoma, n = 14, or nodular hyperplasia, n = 5 were summarized from medical records. CT features for each histologic diagnosis were characterized and analyzed statistically. Common findings in hepatocellular carcinoma included central (79%, P = 0.0030) and marginal enhancement (93%, P = 0.00043) in the arterial phase, cyst-like lesions (93%), capsule formation (93%), and hypoattenuation in the portal (86%), and equilibrium phases (93%). Hepatic adenoma was characterized by a characteristic diffuse enhancement pattern during the arterial phase (57%, P = 0.013), which was also found in nodular hyperplasia (60%), but never in hepatocellular carcinoma. Nodular hyperplasia was less likely to have a capsule structure (20%, P = 0.0087). Mass size was significantly smaller in nodular hyperplasia than in hepatocellular carcinoma and hepatic adenoma (P = 0.0033 and 0.038, respectively). Hyperattenuation in the arterial and the portal phase i.e. contrast retention, was more frequent in hepatic adenoma than in the other groups (P = 0.037 and 0.037, respectively). Nodular hyperplasia was more frequently isoattenuating in the equilibrium phase (P = 0.043)., (© 2012 Veterinary Radiology & Ultrasound.)

Endoscopic polypectomy and argon plasma coagulation (APC) were performed in a refractory case of inflammatory colorectal polyps in a 7-year-old male Miniature Dachshund. Colonoscopic examination revealed a large sessile polyp and multiple diffuse small polyps, localized to the descending colon and rectum. The case showed a poor therapeutic response to prednisolone and cyclosporine. Under anesthesia, piecemeal resections were performed by polypectomy. APC was carried out to cauterize the polyp remnants. After treatment, reduction of the lesions and the improvement in clinical signs were observed, without recurrence of lesions for at least 10 months. Endoscopic treatment by polypectomy and APC is suggested to be a therapeutic option for refractory cases of inflammatory colorectal polyps in dogs.

Medical records of dogs with colorectal polyps were retrospectively reviewed, and clinical presentation of inflammatory colorectal polyps in miniature dachshunds was evaluated. Of 33 dogs found to have colorectal polyps, miniature dachshunds were markedly over-represented with 16 dogs (48%), of which 12 (75%) were found to have inflammatory polyps. Multiple polyps localized between the rectum and the descending colon was the most common finding in miniature dachshunds with inflammatory polyps. Twenty dogs (80%) out of 25 miniature dachshunds with inflammatory colorectal polyps responded to immunosuppressive therapy using prednisolone and cyclosporine. The results of this study indicate that miniature dachshunds are predisposed to develop inflammatory colorectal multiple polyps, for which immunosuppressive therapy may be a treatment option.

Although chemokines and their receptors play an integral role in the regulation of the immune response, there is very little information about their involvement in canine inflammatory bowel disease (IBD). The objective of this study was to evaluate the mRNA expression of 9 selected chemokines and 6 chemokine receptors by real-time reverse transcription PCR in the duodenal mucosa from 21 dogs with IBD and 25 control dogs. The transcription levels of monocyte chemotactic protein-1 (MCP-1)/CCL2, macrophage inflammatory protein-3 alpha (MIP-3α)/CCL20, thymus-expressed chemokine (TECK)/CCL25, mucosae-associated epithelial chemokine (MEC)/CCL28 and IL-8/CXCL8 mRNA in IBD dogs were significantly higher than the corresponding levels in control dogs, but there was no significant difference in the mRNA levels of the chemokine receptors between the 2 groups. In addition, the CCL2 and CXCL8 mRNA levels were significantly higher in the high clinical severity score group than in the low clinical severity score group. However, there was no correlation between chemokine or chemokine receptor mRNA expressions and histopathological severity score. The present results suggest that several chemokines may play important roles in the pathogenesis of canine IBD., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Vincristine induces gastrointestinal motility disorders in humans. Adverse gastrointestinal events are commonly observed in dogs receiving vincristine., Objectives: To evaluate gastric motility after vincristine administration in dogs and the prophylactic effect of a prokinetic agent, mosapride., Animals: Five healthy Beagle dogs., Methods: Five dogs received vincristine i.v. at a dosage of 0.75 mg/m(2). The motility index (MI) of the antral contraction was ultrasonographically evaluated 30 minutes postfeeding before administration of vincristine and for 6 days after vincristine treatment. After a 6-week washout period, the dogs received vincristine with mosapride (2 mg/kg p.o., q24h for 6 days), and the MI was re-evaluated. Adverse gastrointestinal events were evaluated according to the Veterinary Co-operative Group Common Terminology Criteria for Adverse Events (VCOG-CTCAE)., Results: After vincristine administration, a significant decrease (P < .05) in MI was observed on days 3 (6.64 ± 0.30) and 4 (8.02 ± 0.94), compared with pretreatment levels (10.00 ± 0.62). Gastrointestinal adverse events were observed in 4 dogs (grade 2 decreased appetite: 3 dogs; grade 1 vomiting: 2 dogs; and grade 1 diarrhea and grade 2 hematochezia: 1 dog). When mosapride citrate was administered with vincristine and for the next 5 days, no decrease in MI was observed. Furthermore, adverse gastrointestinal events occurred less frequently (grade 1 vomiting and grade 2 hematochezia in 1 dog each)., Conclusions and Clinical Importance: Vincristine (0.75 mg/m(2)) induces gastric hypomotility in dogs. Preventive administration of mosapride citrate (2.0 mg/kg p.o., q24h) improves hypomotility and may decrease the adverse gastrointestinal effects of vincristine., (Copyright © 2011 by the American College of Veterinary Internal Medicine.)

High-mobility group box 1 (HMGB1), a nonhistone chromosomal protein, has recently been suggested as a late mediator of the inflammatory cascade. Blood HMGB1 levels are increased in a number of human diseases, and HMGB1 has been suggested to be a useful marker for disease severity and prognosis. The objective of this study was to assess the clinical usefulness of HMGB1 in dogs. Plasma HMGB1 levels, as well as C-reactive protein (CRP), a typical canine inflammatory marker, were measured in dogs with various diseases, especially systemic inflammatory response syndrome (SIRS), and dogs that had undergone surgery. HMGB1 gradually increased and attained a maximum level 72 hr after surgery, whereas CRP increased rapidly, peaking at 24 hr. Although both HMGB1 and CRP levels were significantly increased in dogs with various diseases compared with the control dogs, no correlation was found between the HMGB1 and CRP values. HMGB1 levels in the SIRS group were significantly elevated compared with those in the non-SIRS group. However, the increase in HMGB1 levels above the reference range was not indicative of SIRS. Instead, the presence of increased HMGB1 and CRP levels above the reference ranges significantly affects the poor outcome of SIRS. The present study indicates that HMGB1 is a novel canine inflammatory marker and is distinct from CRP. However, the additional clinical value of HMGB1 measurement remains unclear, and further studies are warranted.

A 7-year-old Miniature Dachshund presented with severe chronic jaundice and elevated liver enzymes. Destructive cholangitis was diagnosed according to histopathological findings of remarkable ductopenia with inflammatory infiltrates and fibrosis in the portal areas. Supportive therapy with prednisolone, high-dose ursodeoxycholic acid, human placental extract and antibiotics was tried, and the patient showed recovery of clinical signs 3 months after diagnosis. A second liver biopsy was performed about 1 year after initial diagnosis, and bile duct restoration was confirmed with continuous inflammation around portal areas and inside the lobules. Although we could not determine which treatment was effective in this case, destructive cholangitis in dogs may be recoverable with long-term supportive therapies.

Molecular regulation of fibrosis in chronic canine hepatitis is poorly understood. The authors employed quantitative polymerase chain reaction (PCR) to determine the expression levels of genes reported to be related to fibrosis in other species (human, mouse, and rat) and to elucidate the relationship of these genes with the degree of fibrosis and the presence or absence of ascites and/or jaundice in dogs with hepatitis. Nine fibrosis-related genes were assayed: PDGFB, PDGFD, MMP2, TIMP1, THBS1, COL1A1, COL3A1, TGFB1, and TGFB2. Liver samples of 15 dogs with chronic hepatitis and 4 healthy control dogs were obtained via laparoscopic biopsy and subjected to histologic and quantitative PCR analyses. The expression of all 9 genes showed significant positive correlation (P<.01, r>.70) with the degree of fibrosis. Furthermore, the expression levels of all genes except TGFB1 were significantly higher (P<.05) in dogs with hepatic failure-related symptoms (ascites/jaundice). Results suggest that these 9 genes are integral to the development of fibrosis in canine chronic hepatitis., (© The Authors 2011)

We retrospectively studied the clinical and laboratory features and outcomes of chronic enteropathy in Shiba dogs. Among 99 dogs with chronic enteropathy, 21 Shiba dogs (21%) were included in the study (odds ratio, 7.14). No significant differences were seen in signalment, clinical signs, symptoms or laboratory profiles between the Shiba and non-Shiba groups. Severe histopathological lesions in the duodenum were a common finding in the Shiba group. The median overall duration of survival in the Shiba group was 74 days, while that of the dogs in the non-Shiba group could not be determined because more than half of the cases remained alive at the end of this study. The difference between the groups was statistically significant (P<0.0001). The 6-month and 1-year survival rates for the Shiba group were 46% and 31%, respectively. Conversely, the 6-month, 1-year and 3-year survival rates for the non-Shiba group were 83%, 74% and 67%. The results obtained here demonstrated that the Shiba dog is predisposed to chronic enteropathy and shows severe duodenum lesions and poor outcomes, indicating a breed-specific disease.

The paper describes clinical and pathological features of Alexander's disease (AD)-like disorder in a 1 year and 8 months old French bulldog. Clinically, the dog exhibited megaesophagus, emaciation and weakness without any specific neurological symptoms. The dog died of aspiration pneumonia. On the gross observation of formalin-fixed brain, discolored foci were observed in the white matter of the cerebellum and brain stem. Histologically, numerous Rothenthal fibers and hypertrophic astrocytes were distributed especially in the perivascular, subependymal and subpial area of both the cerebrum and cerebellum. The Rosenthal fibers were intensely immunopositive for GFAP and ubiquitin. Demyelination of the white matter was occasionally found in the brain stem. The present case is likely to be categorized in the adult form of AD, though previous AD-like cases in dogs were in the juvenile form.

Canine alimentary lymphoma is currently diagnosed on the basis of findings of cytological or histopathological examination. However, it is often difficult to histopathologically distinguish alimentary lymphoma from lymphocytic-plasmacytic enteritis. Recently, the application of polymerase chain reaction for antigen receptor gene rearrangement (PARR) has been reported. In the present study, we assess the sensitivity of PARR analysis in diagnosing canine alimentary lymphoma using endoscopically obtained biopsy specimens from 12 dogs that were histopathologically diagnosed as having lymphoma. The sensitivity of PARR analysis in diagnosing alimentary lymphoma was found to be 66.7%, which was lower than that of other lymphoid malignancies. A combination of histipathological examination and findings of PARR analysis may improve the diagnostic accuracy.

Blood hyaluronic acid (HA) concentration was measured in dogs with various liver diseases to determine its relationship with histological fibrosis of the liver. The blood HA concentration significantly increased in dogs with chronic liver diseases compared with extrahepatic diseases and control. Furthermore, the median blood HA concentration in dogs with liver cirrhosis (500 microg/l; range, 151-1970 microg/l) was significantly higher than dogs with non-cirrhotic liver diseases (153 microg/l; range, 15-477 microg/l). In histochemical analysis, HA was distributed primarily in the fibrotic area in dogs with chronic liver diseases. As a conclusion, the blood HA concentration was significantly increased in dogs with chronic liver diseases, especially those with cirrhosis. Measurement of the blood HA levels of dogs with suspected liver disease can be a useful diagnostic aid for canine cirrhosis.

Contrast-enhanced ultrasound using Sonazoid, a novel contrast medium with a liver-specific Kupffer phase, was evaluated in canine focal liver lesions Twenty-five dogs with a liver mass were given intravenous Sonazoid, and the enhancement pattern in the arterial, portal, and parenchymal phase was characterized. An enhancement defect in the lesion in the parenchymal phase was observed in all malignant lesions, whereas only one of nine benign lesions had a filling defect. The diagnostic value of the presence of a filling defect for malignancy was statistically significant (100% sensitivity, 88.9% specificity, 94.1% positive predictive value, 100% negative predictive value), and was equal to that of hypoenhancement in the portal or delayed phase. The defect pattern (clear or irregular defect) was dependent (P < 0.05) on the types of malignancy (i.e., hepatocellular carcinoma and other types of malignancies). In the arterial phase, five of the six hepatocellular carcinomas had hypervascularity, whereas no other lesion was characterized by hypervascularity. In some dogs, additional lesions that could not be observed with conventional B-mode ultrasonography were detected in the parenchymal phase. The enhancement pattern of Sonazoid, especially in the parenchymal phase, has potential as a diagnostic tool for canine focal liver lesions.

To investigate the clinical utility of C-reactive protein (CRP) determination in dogs, its plasma concentration was measured by a laser nephelometric method in 928 dogs with various diseases, and was compared with other inflammatory parameters. CRP concentration was elevated in various inflammatory diseases, this was most frequently observed in cases with neoplastic and immune-mediated diseases. All cases of pyometra, panniculitis, acute pancreatitis, polyarthritis, and hemangiosarcoma showed significantly elevated CRP concentrations. On the other hand, the CRP concentration was elevated only in few cases of neurological diseases such as epilepsy, meningoencephalitis, and hydrocephalus and endocrine diseases such as hypothyroidism, hyperadrenocorticism, and diabetes mellitus. Only a weak correlation was observed between the CRP concentration and white blood cell (WBC) counts (r=0.44) but no correlation with band neutrophil counts. There was no correlation between the CRP and albumin concentrations, but a weak negative correlation (r=-0.40) when excluding chronic intestinal diseases and nephrotic syndrome, which can cause protein loss. Thus, CRP can be useful to detect inflammations that cannot be detected by WBC and, or band neutrophil counts, suggesting that the examination of CRP concentration is essential as routine diagnostic test.

Lymphocytic-plasmacytic enteritis (LPE) is a type of canine inflammatory bowel disease (IBD). One of its most probable causes is a defect in the mucosal permeability barrier. In the present study, intestinal permeability in LPE dogs was examinated to evaluate its clinical value. Twenty-nine dogs with LPE diagnosed by clinical and histological examinations were included in this study. Intestinal permeability was evaluated by measuring the ratio of the concentrations of two sugars (lactulose (L) and rhamnose (R)) with different molecular weights in urine samples after oral administration of a solution containing them. Biopsy specimens of duodenum were evaluated according to histological criteria. The urinary L:R ratio in the 29 LPE dogs (1.68 +/- 1.17, mean +/- SD) was significantly higher than that in the 10 healthy control dogs (0.75 +/- 0.38, P<0.01). In the LPE dogs, a weak correlation was observed between the histopathological grading score of the duodenum and the urinary L:R ratio (r=0.408, P<0.05). The urinary L:R ratio in the 20 dogs showing hypoalbuminemia (< 2.5 g/dl) was significantly higher than that in the 9 dogs with normal serum albumin levels > 2.5 g/dl (P<0.01). In conclusion, permeability of the intestinal mucosa as determined by the urinary L:R ratio could be a useful laboratory parameter for evaluating intestinal damage in LPE dogs.

To investigate the clinical utility of C-reactive protein (CRP) in idiopathic polyarthritis (IPA), its concentration was measured in dogs with IPA. The CRP concentration was markedly increased in all the IPA dogs at the time of diagnosis and decreased significantly in response to the initial corticosteroid treatment; this indicated that CRP can be used as an index for therapeutic response in IPA cases. Furthermore, at 6 months after the diagnosis, a significant association was observed between the CRP concentration at follow-up (6-13 days after the treatment was started) and the frequency of medication ("no or seldom-medicated (NSM)" groups or "continuing medication (CM)" groups). These results suggest that the initial response of CRP to corticosteroid treatment may be a prognostic factor of canine IPA.

Prognostic factors associated with survival in dogs with lymphocytic-plasmacytic enteritis (LPE) were investigated through a retrospective study. Using case records, 48 dogs diagnosed with LPE were classified as survivors (n = 32) or non-survivors (n = 16), and the clinical and clinicopathological parameters were reviewed between the 2 groups by using univariate and multivariate prognostic analysis. Compared to the hospital population, non-survivors had an overrepresentation of the Shiba breed. Results of univariate analysis indicated that anorexia, severe weight loss, packed cell volume, and total protein were significantly associated with survival for 6 months after diagnosis. In multivariate analysis, anorexia and hypoproteinemia were significantly associated with survival. Furthermore, initial response to treatment was strongly associated with poor prognosis. Based on these clinical and laboratory parameters such as anorexia, hypoproteinemia and initial response to treatment, it may be possible to predict poor prognosis in canine LPE.

Skin biopsy specimens from face, axilla, abdomen and thigh, mucocutaneous tissues from anus and vagina, and oral mucosa from six healthy Beagle dogs were examined for desmoplakin (Dsp) immunoreactivity using immunoblotting and immunohistochemical analysis. With immunoblotting using mouse antihuman Dsp 1 monoclonal antibody (DP2.17), a band was detected at 250 kDa in all the extracts as in normal human skin samples, although no band was detected at 210 kDa, suggesting that monoclonal antibody DP2.17 recognizes canine Dsp 1 but not Dsp 2. Moreover, the desmosome regions of all specimens were stained with DP2.17 using immunohistochemical analysis. From these results, DP2.17, developed for the examination of human skin, might be suitable for the investigation of Dsp-related skin disorders in dogs.

The electrophoretic mobility and the immunologic specificity of erythrocyte pyruvate kinase (PK) of the homozygous Basenji dog with PK deficiency were identical to those of normal M2-type PK isozyme seen in the white cell but not to those of the erythrocyte PK isozyme. Kinetic properties and stability were also consistent with the M2-type PK isozyme. Defective PK in the homozygous red cell was due to the absence of the erythrocyte PK isozyme and the compensatory presence of M2-type PK isozyme, as seen in the severe classical type PK deficiency in man.